Hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation: experience in a pediatric oncological institution. / Cistitis hemorrágica tras trasplante alogénico de progenitores hematopoyéticos: experiencia en un centro oncológico pediátrico.

OBJECTIVE: To analyze the risk factors associated with hemorrhagic cystitis (HC) severity and the treatment strategies available in HC patients following allogeneic hematopoietic stem cell transplantation (AHSCT). MATERIALS AND METHODS: A retrospective study of medical records was carried out. Patients with HC following AHSCT treated from 2017 to 2021 were divided into two groups according to severity -mild and severe. Demographic data, disease-specific characteristics, urological sequelae, and overall mortality were compared between both groups. The hospital's protocol was used for patient management. RESULTS: 33 episodes of HC were collected in 27 patients, 72.7% of whom were male. HC incidence following AHSCT was 23.4% (33/141). 51.5% of HCs were severe (grades III-IV). Severe graft host disease (GHD) (grades III-IV) and thrombopenia at HC onset were associated with severe HC (p= 0.043 and p= 0.039, respectively). This group had longer hematuria times (p< 0.001) and required more platelet transfusions (p= 0.003). In addition, 70.6% required bladder catheterization, but only 1 case needed percutaneous cystostomy. None of the patients with mild HC required catheterization. No differences were found in terms of urological sequelae or overall mortality. CONCLUSIONS: Severe HC could be predicted thanks to the presence of severe GHD or thrombopenia at HC onset. Severe HC can be managed with bladder catheterization in most of these patients. A standardized protocol may help reduce the need for invasive procedures in patients with mild HC.

OBJETIVO: Analizar factores de riesgo asociados a la gravedad de la cistitis hemorrágica (CH) y estrategias de tratamiento en pacientes con CH tras trasplante alogénico de progenitores hematopoyéticos (TAPH). MATERIAL Y METODOS: Estudio retrospectivo de historias clínicas. Los pacientes con CH tras TAPH tratados entre 2017 y 2021 se dividieron en dos grupos según la gravedad del cuadro (leve y grave). Se compararon datos demográficos, características específicas de la enfermedad, secuelas urológicas y mortalidad global entre ambos grupos. Se utilizó el protocolo del hospital para el manejo de los pacientes. RESULTADOS: Se recogieron 33 episodios de CH en 27 pacientes, de los cuales el 72,7% fueron varones. La incidencia de CH tras TAPH fue del 23,4% (33/141). El 51,5% de las CH fueron graves (grados III-IV). La enfermedad de injerto contra huésped (EICH) grave (grados III-IV) y la trombopenia al inicio se asociaron a CH grave (p= 0,043 y p= 0,039, respectivamente). Este grupo tuvo mayor tiempo de hematuria (p< 0,001) y necesitó más transfusiones de plaquetas (p= 0,003). Además, el 70,6% precisó sondaje vesical, pero solo un caso cistostomía percutánea. Ningún paciente con CH leve precisó sondaje. No hubo diferencias en las secuelas urológicas ni en la mortalidad global. CONCLUSIONES: Una CH más grave podría predecirse por la presencia de EICH grave o trombopenia al inicio del cuadro. La CH grave puede manejarse con sondaje vesical en la mayoría de estos pacientes. Seguir un protocolo estandarizado puede reducir la necesidad de procedimientos invasivos en pacientes con CH leve.

Pediatric perianal Crohn's disease behavior in the era of biologic therapy. / Comportamiento de la afectación perianal en pacientes pediátricos con enfermedad de Crohn en la era de la terapia biológica.

AIM OF THE STUDY: To describe perianal Crohn's disease behavior and the role of biological therapy in a sample of pediatric patients. METHODS: A retrospective study of pediatric patients with Crohn's disease (CD) treated in our institution from 2017 to 2021, with a minimum follow up period of 6 months, was conducted. Patients were divided whether they had perianal disease (PD) or not. Baseline characteristics, extension of disease, growth failure rate, aggressive pattern rate, use of biological therapy and need for surgery, among other variables, were compared between both groups. Clinical and/or radiological improvement in the last 6 months of follow up was considered good control of PD. RESULTS: Seventy eight pediatric patients with CD were included. Median age at diagnosis was 10.5 years, and median follow up time was 3.8 years. 64.1% patients were male. Of all, 15 (19.2%) had perianal disease, of which 10 had fistulizing findings and 5 had non fistulizing findings. PD was presented at diagnosis in 8 patients, and the rest developed it in a median time of 1 year from diagnosis. PD was associated with growth failure (p = 0.003), use of biological therapies (p = 0.005), and need for second line of biologics (p = 0.005). Most patients (12/15, 80%) had good control of PD with the treatment received. CONCLUSIONS: CD patients with PD seem to need a more aggressive treatment, with biological therapies playing a key role for its handling nowadays. These patients require close nutritional evaluation that ensures proper development and growth.

OBJETIVO DEL ESTUDIO: Describir el comportamiento de la enfermedad de Crohn perianal y el papel de la terapia biológica en una muestra de pacientes pediátricos. METODOS: Estudio retrospectivo de pacientes pediátricos con enfermedad de Crohn (EC) tratados en nuestro centro entre 2017 y 2021, con un seguimiento mínimo de seis meses. Los pacientes se dividieron en función de si tenían enfermedad perianal (EP) o no. Se compararon entre ambos grupos las características iniciales, la extensión de la enfermedad, el índice de retraso en el crecimiento, el índice de patrón agresivo, el empleo de terapia biológica y la necesidad de cirugía, entre otras variables. Se consideró un buen control de la EP una mejoría clínica o radiológica en los 6 últimos meses de seguimiento. RESULTADOS: Se incluyeron 78 pacientes pediátricos con EC. La edad mediana en el momento del diagnóstico fue de 10,5 años, y el tiempo mediano de seguimiento fue de 3,8 años. El 64,1% de los pacientes eran varones. Del total, 15 (19,2%) tenían enfermedad perianal, de los cuales 10 presentaban hallazgos fistulizantes y 5 no fistulizantes. La EP estaba presente en el momento del diagnóstico en 8 pacientes, y el resto la desarrolló en una mediana de 1 año desde el diagnóstico. La EP se asoció con retraso en el crecimiento (p = 0,003), empleo de terapias biológicas (p = 0,005) y necesidad de una segunda línea de terapia biológica (p = 0,005). La mayoría de los pacientes (12/15, 80%) tuvieron un buen control de la EP con el tratamiento recibido. CONCLUSIONES: Los pacientes de EC con EP parecen necesitar un tratamiento más agresivo, en el que las terapias biológicas desempeñan hoy en día un papel fundamental. Estos pacientes precisan de una estrecha evaluación nutricional que garantice su correcto crecimiento y desarrollo.

[Preoperatory sonography efficiency in paediatric patients with cholelithiasis undergoing laparoscopic cholecystectomy]. / Eficacia de la ecografía preoperatoria en la colelitiasis en pacientes pediátricos sometidos a colecistectomía laparoscópica.

INTRODUCTION: Biliary lithiasis is not much frequent in paediatric patients. The manegement of cholelithiasis in patients undergoing laparoscopic cholecystectomy is still controversial. We propose the preoperatory echographic study of the biliary tree 24-48 h before surgery, as the first choice, instead of the intraoperatory cholangiography. MATERIAL AND METHODS: We made a retrospective study of 42 patients undergoing laparoscopic cholecystectomy due to symptomatic biliary lithiasis during the last 15 years, with ages between 18 months and 17-years-old (mean age 9,6-years-old) and weight between 11 and 70 kg (mean weight 42 kg) at the moment of surgery. Six of them had haematological illnesses, 17 came to the hospital because of acute abdominal pain, 10 had been studied because of recurrent abdominal pain and 9 had casual diagnoses. Abdominal sonography was performed in all patients 24-48 hours before surgery. RESULTS: Four children were diagnosed of biliary duct lithiasis: two choledocolithiasis and two stones in the cystic duct. One of the cystic stones was extracted in the operating room and the rest resolved spontaneously. One patient presented dilatation of choledocal duct after surgery, without any stones' evidence. Also this patient resolved spontaneously. We had no complications. CONCLUSIONS: Biliary lithiasis is not frequent in children, even if it seems to be increasing. A few of these patients will suffer of choledocolithiasis. The intraoperatory exploration of the biliary tree during laparoscopic surgery is technically difficult due the small size of paediatric patients. Cholangiography is not always successful and can produce some important complications as pancreatitis. Preoperative sonography 24-48 hours before surgery is a safe and efficient method for the diagnosis and follow-up of paediatric patients with biliary lithiasis undergoing laparoscopic cholecystectomy. It is safe enough to be performed without intraoperatory cholangiography.

Non stenotic food impaction due to eosinophilic esophagitis: a potential surgical emergency.

AIM: Eosinophilic esophagitis (EoE) is an emergent condition in which a mucosal infiltrate of > 20 eosinophils per high power microscopic field is accompanied by motor disturbances that may cause food impaction in the absence of esophageal stricture. We report a series of such cases to point out the potential involvement of pediatric surgeons in diagnosis and treatment. Furthermore, data on the motor function of the esophagus investigated manometrically is included. MATERIAL AND METHODS: Thirteen patients with EoE were referred to our emergency room for acute food bolus impaction. Their median age at diagnosis was 12 years (range 7.6-14.4). History of allergy, endoscopy with biopsy and esophageal function (24-h combined ambulatory manometry with simultaneous pH-metry) were investigated. RESULTS: In 7 patients emergency endoscopic extraction of the impacted bolus was necessary. Allergic tests were positive in eight patients. The pH probe showed gastroesophageal reflux in two cases. Upon endoscopy, typical features of EoE (esophageal trachealization and whitish papular exudates) were found. Ambulatory 24-h manometry revealed abnormal motility of the distal esophagus with strikingly high amplitudes (> 150 mmHg) and long duration (> 7 sec) of the waves, particularly during the night. Six patients responded rapidly to steroids and/or antiallergic treatment. The remaining patients had a good outcome with dietary treatment alone. CONCLUSIONS: EoE is an emergent condition that may involve the pediatric surgeon in both the diagnosis and treatment. Typical endoscopic findings and biopsy are required for proper diagnosis. Ambulatory manometry reveals a marked propulsive dysfunction that explains impaction. This dysfunction is reversible, since the symptoms usually disappear with steroids or antiallergic treatment.

[Recurrence and spontaneous remission of nephrotic syndrome in secondary renal amyloidosis]. / Recurrencia y remisión espontánea de síndrome nefrótico en amiloidosis renal secundaria.

Secondary systemic amyloidosis (AA) occurs in association with chronic inflammatory disorders and chronic infections. Regression can occur after therapeutically induced remission of the underlying disease; spontaneous remissions has been reported infrequently. We report a 61 year-old woman, with antecedent pulmonary tuberculosis, who developed a nephrotic syndrome at the time of a respiratory infection. Renal biopsy showed secondary amyloidosis. Remission in the nephrotic syndrome appeared spontaneous, but it recurred in the course of pneumonia, and had a second spontaneous remission a maintained at present.

[Progressive systemic sclerosis associated with anti-myeloperoxidase ANCA vasculitis with renal and cutaneous involvement]. / Esclerosis sistémica progresiva asociada a vasculitis ANCA anti-mieloperoxidasa con afectación renal y cutánea.

Sclerodema renal crisis is the usual form of presentation of renal disease in systemic sclerosis. We report a woman who at age 63 was given a diagnosis of scleroderma with Raynaud's phenomenon and cutaneous, oesophageal and lung involvement but no evidence of renal disease and no treatment with D-penicillamine. Two years later she developed progressive renal failure, nephrotic range proteinuria, haematuria and the presence of serum MPO-ANCA; she was normotensive. Renal biopsy revealed extracapillary and necrotizing glomerulonephritis and skin biopsy showed leucocytoclastic vasculitis. This clinical picture was compatible with necrotizing vasculitis of the microscopic polyarterits type. After treatment with pulse steroids followed by oral steroids and monthly intravenous cyclophosphamide her renal function stabilised and the serum MPO-ANCA disappeared.

[Prevalence of genetic prothrombotic factors (factor V Leiden and II20210 prothrombin mutation) in glomerular nephropathies with or without thrombosis]. / Prevalencia de factores protrombóticos de base genética (factor V Leiden y mutación II20210 de la protrombina) en nefropatías glomerulares con o sin trombosis.

The presence of genetic prothrombotic factors (factor V Leiden and the prothrombin II20210 mutation) was investigated in 38 patients with glomerulonephritis with or without a history of thrombotic events and/or nephrotic syndrome. We found an increased prevalence (36%) of heterozygous factor V Leiden in those patients with a history of thrombotic events. This is ten times the prevalence in the normal Spanish population. Carrier status for this mutation may be a determining factor in the development of thrombotic events along with the acquired disorders of coagulation to which these patients are prone. We found only one patient who was a carrier of the G-A II20210 mutation of the prothrombin gene; this patient had no history of venous thrombosis or embolism. Our findings suggest the need to measure activated protein C resistance and to look for the most frequent genotype causing it, Factor V Leiden, in patients with glomerulonephritis to identify those at risk who may benefit from prophylaxis against thrombosis.

Prevalence of hepatitis C antibodies (HCV) in a dialysis population at one center.

Hepatitis C (HC) has been recently diagnosed by determination of specific antibodies that represent the former so-called non-A, non-B hepatitis. We studied the prevalence of plasma HCV antibodies among 61 unselected patients on hemodialysis (HD) and 43 on continuous ambulatory peritoneal dialysis (CAPD). Plasma C-antibodies were determined through the ELISA test system. Transfusion policy was the same in both groups. The prevalence of hepatitis C virus antibodies was significantly higher in hemodialysis patients than among those on CAPD. Time on dialysis, previous blood transfusions, and renal transplantation seem to increase the prevalence of C hepatitis antibodies among hemodialysis patients. The effect of these parameters on CAPD was smaller. Understanding the reasons for these differences may help prevent this disease among dialysis patients.

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-I (PAI-I) levels in plasma and peritoneal effluent in patients on CAPD.

The formation of fibrin on peritoneal surface has been related to the appearance of adhesions both, in surgical and CAPD patients. It is known that mesothelial cells have fibrinolytic activity related with t-PA production. We studied plasma and overnight peritoneal effluent (OPE) from 20 CAPD stable patients. Antigenic PAI and t-PA were determined. These values and its correspondent peritoneal saturation indexes were compared to urea and creatinine MTCs, peritonitis incidence, UF capacity, protein losses, Pi, Ca, Na, CO2t, urea and creatinine OPE levels. Plasma t-PA 6.64 +/- 4.68 (2.4-20); Plasma PAI-I 24.8 +/- 17.1 (p < 0.001 in respect to controls) (4-62); OPEt-PA 1.46 +/- 0.95 (0.4-4.6); OPE PAI-I 7.3 +/- 5.6 (0-20.4). Peritoneal saturation ratios were for t-PA 29.6 +/- 21% (6-65) and for PAI-I 34 +/- 32% (7-132). In conclusion our data do not support strong relationship between peritoneal t-PA/PAI system and the functional characteristics of the peritoneal membrane although plasma PAI-I, after an increase in patients at early stages on CAPD, shows a tendency to decrease over time and frequent peritonitis. The values of peritoneal saturation ratios for t-PA/PAI are higher than expected for their molecular weight, which suggests local production. An elevated plasma t-PA levels has been found in older patients.

Staphylococcus aureus nasal carrier status (SANCS) in CAPD patients; is it induced or favored by subcutaneous rHu-erythropoietin?

Staphylococcus aureus nasal carriage status (SANCS) has been recognized as a risk factor for patients on CAPD, due to a higher probability of suffering peritoneal catheter infections. The use of subcutaneous drugs (insulin dependent diabetics, drug addicts, HD patients and antiallergic vaccines), has been associated with increased risk of SANCS. On CAPD, erythropoietin (EPO) is almost universally used by the subcutaneous route. The objective of this paper was to evaluate the incidence and prevalence of SANCS in 85 CAPD patients by means of nasal smear and the influence of SANCS on peritoneal and catheter infection rate. Patients were divided in four groups according to diabetic status and EPO treatment (mean dose 2000 u. twice a week). The prevalence of SANCS in control groups was 30% in non-diabetics and 23% in diabetics. EPO treated patients showed a prevalence of SANCS of 39% in non-diabetics and 45% in diabetics due to the presence of 7 and 5 carrier patients respectively. SANCS patients (29% of the population), suffered 45% of peritonitis and 42% of exit-site infections caused by S. aureus. In a prospective part of the study, there was no difference in the frequency of developing positive cultures among EPO and control (30% of patients). No male EPO treated patients developed SANCS. We conclude that it is necessary to monitor S. aureus nasal carrier status periodically in CAPD patients especially in women. Whether or not subcutaneous erythropoietin treatment is implicated pathogenetically with SANCS, is not clarified by our data because of the frequent spontaneous appearance of SANCS among CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Medium term response to H-R erythropoietin in CAPD patients: the influence of erythropoietin plasmatic levels and the effects on peritoneal transport capacity.

Anemia of CRF has been corrected by use of H-R-EPO both in hemodialysis and CAPD patients. Long term response to subcutaneous EPO and its relationship with serum EPO levels remain to be established. Twenty-five CAPD patients treated with CAPD during 30 +/- 28 (mean +/- SD) months were included in this study. The follow-up period was 6-24 months. All patients have been on CAPD at least 6 months and their Hemoglobin (Hb) level was lower than 8.5 g/dl. Twelve patients received EPO by subcutaneous route, at doses of 20 u./Kg daily and 13 other patients at doses of 2000 units twice a week. Thereafter, these doses were adjusted to obtain a Hemoglobin level ranging 10.5-13 g/dl. In conclusion, our results suggest that the subcutaneous route for H-R-Erythropoietin can be considered as the best choice for CAPD patients. Low doses twice a week seem to improve anemia in 2 months. Later, dose adjustment should be done according to the patient's response. The improvement in nutritional status we observed suggests a new positive aspect for EPO therapy. Our data did not show changes in peritoneal function.

Characterisation of the mitogenic-induced capacity of peritoneal effluent on human and mice fibroblasts in culture.

During continuous ambulatory peritoneal dialysis, solutes capable of stimulating fibroblast activity could be transferred into dialysate; their significance and consequences remain to be established. Sixty-three stable non-selected patients on CAPD were included in this study. Peritoneal transport for water and small solutes was assessed. To explore the mitogenic-induced capacity of peritoneal nocturnal effluent, 50 microliters were added to culture plates of mice and human fibroblasts. Peritoneal effluent alone shows a mitogenic potency slightly greater than insulin and clearly less than bovine fetal serum. When coadjuvants are added, mitogenicity increases but in a variable manner among patients. No differences can be observed in relation to diabetes mellitus, time on CAPD, previous peritonitis, and losses of diffusion capacity. We noted significant inverse linear correlations between mitogenicity value and ultrafiltration, effluent calcium, and creatinine. Neither adrenergic nor calcium-channel blockers influenced these values. We conclude that the peritoneal effluent of CAPD patients has a variable effect on fibroblast growth. Some of the blood components seem to be implicated in this activity. Reduced peritoneal ultrafiltration capacity, probably by a concentration mechanism, is related to a greater mitogenic potency in peritoneal effluent. CAPD patients with impaired ultrafiltration may be at high risk for autoactivation of peritoneal fibroblasts, mainly in mesothelial denudate states.

Measurement of the peritoneal platelet activity through the effluent betathromboglobulin levels in CAPD patients.

Platelet activity is closely related to endothelium and could release factors able to influence capillary wall and surrounding tissues. BTG is a protein included in platelet vesicles and a measure of its activation. Some alterations of peritoneum could be partially related to platelet activity. BTG peritoneal transport from blood is weight limited (36000) and consequently, high levels in effluent should represent local production. The aim of this study has been to characterize peritoneal effluent BTG.12 patients, on CAPD 27 +/- 15 mon., 5 diabetics were studied. Previous peritonitis was 0.3 +/- 0.4 e/year. Determinations performed: Plasma (P) (BTG, T. protein, albumin, platelet count, Hcto and Fibrinogen) and Effluent (EF) (BTG, T. protein, Fibrinopeptide A, FDP, Fibrinolytic act., Fibrinogen, Plasminogen and Mitogenic induced capacity on Swiss 3T3 mice fibroblasts). To evaluate peritoneal function we used mass transfer coefficients (MTC) and net UF.R.:BTG levels: P 118 +/- 14 EF 34 +/- 14 ng/ml P/EF (%) 31 +/- 13 (6-54%). Regression analysis: P BTG did not show significant relationship with any of the studied parameters. EF BTG showed direct significant correlation (p less than 0.05) with Creatinine-MTC (r: 0.81) and EF Fibrinogen (0.68) and in the limit of significance with EF T. prot (0.57) and EF Mitogenicity (0.62). P/EF BTF showed significant correlation with creatinine-MTC (0.77). The analysis of these values grouping patients showed: diabetes has no influence on BTG values, hypertensive patients show higher P/EF BTG values than normotensive (39 +/- 9 vs 23 +/- 11%, p less than 0.05) and no influences of peritonitis or CAPD period were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of the anemia with human recombinant erythropoietin in CAPD patients.

Three homogenous groups of CAPD patients, all of them with plasma hemoglobin levels lower than 8 g/dl were studied. Group 1 included 8 patients who received EPO by the subcutaneous route (s.c), at doses of 20 u./kg daily; this dose was reduced when a hemoglobin level higher than 10.5 g/dl was reached. Group 2 included 7 patients treated with EPO by subcutaneous route but at doses of 2000 units twice a week. Group 3 was constituted by 4 patients receiving EPO by intraperitoneal route (i.p.), at doses of 4000 u/day, three days a week. All patients showed an increase in hematocrit and Hb levels after three months of treatment, but the mean EPO dose was quite different comparing the groups, maintaining the reached levels at the 9th month; reticulocyte count increased only during the first month. The rest of clinical and biochemical parameters did not suffer any significant modifications. Our features showed a higher profit, that is, higher increase in Hb level with lower dose of EPO in the s.c. group in respect to i.p. group. Furthermore, we have registered a marked increase in the frequency of exogenous peritonitis in these particular patients while using i.p. EPO. In conclusion, we feel that subcutaneous route for H-R-Erythropoietin is an ideal way for this treatment, resulting in a more adequate profit ratio than that described in hemodialysis patients. The intraperitoneal route is more expensive and risky for the peritoneum, probably as a consequence of the increase of manipulations.

Characteristics of the peritoneal mass transfer of parathormone in patients under continuous ambulatory peritoneal dialysis therapy.

Recent studies have shown that the mass transfer coefficients (MTC) for low- and middle-molecular-weight substances are maintained at medium terms in patients under continuous ambulatory peritoneal dialysis (CAPD) therapy. We have studied the MTC for parathormone (MW 5,500-6,000) in 29 patients under CAPD. 11 patients were assessed once, 9 patients were assessed twice, and 9 were assessed three times, with 6-month intervals between assessments; in 15 cases nitroprusside (4.5 mg/l) was added to the dialysate, and in 2 cases the assessment was carried out during an episode of peritonitis. A bicompartmental model with exponential ultrafiltration was used, and the generation rates were calculated by mass balance. The MTC was calculated by minimization of the quadratic error, following the procedure of Runge and Kutta. The mean MTC values were 21.2 +/- 5.9 for urea, 10.26 +/- 5.9 for creatinine 2.8 +/- 1.8 for inulin and 1.0 +/- 0.8 for parathormone (PTH), with significant correlation between the MTC values for PTH and inulin (r = 0.5, p less than 0.01). There is a direct correlation between MTCPTH and peritoneal PTH clearance, and an inverse one between MTCPTH and serum PTH, with r = 0.8 and 0.51, respectively. No correlation was found between the MTC for inulin or PTH and the duration of the CAPD therapy, nor with the number of episodes of peritonitis. No significant medium-term variations were detected in the MTC values for PTH and inulin. Both peritonitis and the intraperitoneal administration of nitroprusside induce significant increases in the MTCPTH.